Our study was to compare the therapeutic outcomes of radiofrequency ablation (RFA) with or without conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) within Milan criteria in subcapsular versus nonsubcapsular locations by using propensity score matching.

This retrospective study included 171 consecutive HCC patients meeting Milan criteria who initially received RFA with or without cTACE at a tertiary academic center between January 2017 to December 2022. Technical success rate, progression-free survival (PFS) were recorded. Factors predicting PFS after RFA with or without cTACE were investigated through a Cox proportional hazard model.

The cumulative 1-, 3-, and 5-year PFS were 73.9%%, 27.7%%, and 7.7%, respectively. The cumulative PFS rates were 76.1% and 17.3% at 1 and 3 years, respectively, in the subcapsular group and 71.8% and 37.2% in the nonsubcapsular group (p = 0.034). Matching yielded 49 matched pairs of patients. In the matched group, corresponding cumulative PFS rates were 75.6% and 14.6% at 1 and 3 years, respectively, in the subcapsular group and 69.6% and 30.2% in the nonsubcapsular group (p = 0.156). Multivariate analysis confirmed that subcapsular tumor location was not an independent risk factor for PFS. Additionally, differences in technical success rate were not significant between groups.

The differences in PFS rates and technical success rate in HCC patients within the Milan criteria who received RFA with or without cTACE were not significant between the subcapsular and non-subcapsular groups. Future larger prospective multicenter trials are needed to validate these findings.

Central bile duct invasion (BDI) by hepatocellular carcinoma (HCC) is rare and associated with poor prognosis, lacking treatment guidelines. While transarterial chemoembolization (TACE) is often used for unresectable cases, determining optimal candidates post-biliary drainage is controversial. We aim to develop a prognostic prediction model for unresectable HCC (uHCC) patients with central BDI receiving sequential TACE after successful biliary drainage.

We retrospectively analyzed 267 uHCC patients with central BDI receiving successful biliary drainage and sequential TACE from seven tertiary centers (2015-2021), divided into training (n=187) and validation (n=80) sets. Using Cox proportional-hazards regression model, we identified key prognostic indicators for overall survival (OS) and constructed a prediction model.

Pre-TACE total bilirubin (TBil) values, extrahepatic spread (EHS), multiple intrahepatic tumors (MIT), and portal vein tumor thrombus (PVTT) were identified as the significant clinical indicators for OS. These four parameters were included in a novel prediction model, named TEMP score, which could successfully categorize patients in the training set into three distinct risk grades with median OS of 26.9, 9.4, and 5.8 months, respectively. The TEMP score predicted the time-dependent areas under the receiver operating characteristic curves for OS at 6 months, 1 year, and 2 years of 0.813/0.907, 0.833/0.782, and 0.838/0.811 in the training and validation sets, with corresponding C-indices of 0.812/0.929, 0.829/0.761, and 0.818/0.791, respectively, outperforming other currently available models in both cohorts. The calibration curve of the model for predicting OS presented good consistency between observations and predictions in both the training set and validation set.

The TEMP score effectively stratifies the prognosis of uHCC patients with central BDI who have undergone successful bile drainage and sequential TACE, helping to identify those who may benefit from TACE treatment.

The objective was to describe the dynamics of noninvasive tests (NITs) in cirrhotic patients following sustained virological response (SVR) and to assess their correlation with hepatocellular carcinoma (HCC) risk.

The dynamics of NITs (Fib4, APRI and LSM) were described in patients with cirrhosis after SVR included between 2006 and 2015 in two prospective French multicentre cohorts (ANRS CO22 Hepather and CO12 CirVir). To assess their relationship with the risk of HCC, a joint modeling approach was employed using both standard and flexible models adjusted for age and sex. The impacts of NIT current value and slope during follow-up on HCC risk were assessed taking into account competing risks of death.

3067 patients with cirrhosis who achieved SVR were analyzed, among whom 228 (7.4%) developed HCC and 210 (6.9%) died during a 26-month follow-up. All NITs were increased at baseline in patients who ultimately developed HCC, whereas platelet counts were lower. All NITs improved in patients who did not develop HCC. More contrasted changes were observed during the follow-up of patients who ultimately developed HCC. Joint model analyses showed that current values of Fib4, APRI and platelet count at any time impacted HCC risk. Only Fib4 and APRI slopes influenced the same outcome. When considering NIT current value and slope simultaneously, only the current value of NITs impacted HCC risk while the slopes were not informative.

The dynamics of NITs following SVR do not identify cirrhotic patients who could be safely excluded from surveillance programmes. NIT current value is more informative than slope which would necessitate to regularly re-assess HCC risk to design individualized surveillance strategies.

It has been postulated that that monitoring noninvasive tests (NIT) dynamics following HCV cure may inform on HCC residual risk in patients with cirrhosis, and may allow for the discontinuation of surveillance in certain patient subsets. We analyzed data from over 3,000 patients and found that while all NITs improved in cirrhotic patients who did not develop HCC, those who eventually developed liver cancer showed more contrasted changes in these tests. Specifically, the current values of tests like Fib4 and APRI were linked to an increased risk of HCC. while their slopes did not provide additional useful information, suggesting that dedicated prospective studies are warranted to define how repeated measurement of NIT could be combined with other variables into HCC risk stratification algorithms. Until then, HCC surveillance should be maintained in all patients with cirrhosis following HCV eradication, even in case of decreased NIT.

While the CT-based method of detecting clinically significant portal hypertension (CSPH) emerged as a noninvasive alternative for evaluating CSPH, its predictive ability for post-hepatectomy outcomes is unknown. Therefore, this study aimed to evaluate the impact of CT-based CSPH on outcomes following hepatectomy for hepatocellular carcinoma (HCC).

This retrospective single-center study included patients with advanced chronic liver disease (ACLD) who underwent hepatectomy for very early or early-stage HCC between January 2017 and December 2018. CSPH was assessed using CT-based criteria, which included splenomegaly determined by deep learning-based spleen volume measurements with personalized reference thresholds, and the presence of gastroesophageal varices (GEV), spontaneous portosystemic shunt or ascites. Logistic regression and competing risk analyses were used to identify factors associated with severe post-hepatectomy liver failure (PHLF), hepatic decompensation, and liver-related death or transplantation. The predictive performance of existing models for PHLF was compared using both CT-based and conventional CSPH criteria (endoscopic GEV or splenomegaly with thrombocytopenia).

Among 593 patients (460 men; mean age 57.9 ± 9.3 years), 41 (6.9%) developed severe PHLF. The median follow-up period was 62 months. CT-based CSPH independently predicted severe PHLF (OR 7.672 [95% CI 3.209-18.346]), hepatic decompensation (subdistribution hazard ratio (sHR) 4.518 [1.868-10.929]), and liver-related death or transplantation (sHR 2.756 [1.315-5.773]). When integrated into existing models, CT-based CSPH outperformed conventional CSPH in predicting severe PHLF (AUC 0.724 vs. 0.694 for EASL algorithm (p = 0.036) and 0.854 vs. 0.830 for Wang's model (p = 0.011)).

CT-based CSPH is a strong predictor of poor post-hepatectomy outcomes in HCC patients with ACLD, offering a noninvasive surgical risk assessment tool.

Question Can CT-based detection of clinically significant portal hypertension (CSPH) serve as a noninvasive predictor of post-hepatectomy outcomes in hepatocellular carcinoma (HCC) patients? Findings CT-based CSPH independently predicted severe post-hepatectomy liver failure, hepatic decompensation, and liver-related death or transplantation, outperforming conventional CSPH criteria in predictive performance. Clinical relevance CT-based CSPH offers a noninvasive and effective tool for surgical risk assessment in HCC patients, potentially improving the selection of candidates for hepatectomy and optimizing patient outcomes.

Hepatocellular carcinoma is a tumor of epithelial origin that arises from the action of different carcinogens on the hepatocytes and has a high worldwide incidence. The prognostic markers of this disease have not been completely established. Mutations in the gene encoding β-catenin are overexpressed in hepatocellular carcinoma. The objective of our study was to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the already known prognostic markers.

We conducted an observational and prospective cohort study on adult patients diagnosed with hepatocellular carcinoma from whom samples of nontumor and tumor liver parenchyma were taken intraoperatively to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the known prognostic markers.

A total of 81 samples were collected, of which 48 met the inclusion criteria. The final sample was divided into patients with a diagnosis of hepatocellular carcinoma on a cirrhotic liver, corresponding to 31 patients (64.6%), and patients with a diagnosis of hepatocellular carcinoma on a noncirrhotic liver, corresponding to 17 patients (35.4%). We found that overexpression of β-catenin and the neutrophil/lymphocyte ratio are independently related to disease-free survival, and both overexpression and molecular repression of β-catenin are independently related.

Molecular overexpression of β-catenin in hepatocellular carcinoma compared with nontumor tissue is associated with worse disease-free survival, and its combination with a high neutrophil-lymphocyte ratio worsens this prognosis.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

Although several therapeutic agents show efficacy in advanced hepatocellular carcinoma (HCC), biomarkers such as comprehensive genomic profiling (CGP) for the selection of second-line treatments after immunotherapy have not been established. We evaluated the value of CGP for the treatment decision in patients with HCC.

We retrospectively studied 52 patients with advanced HCC who received CGP tests at three tertiary hospitals between February 2022 and November 2023. Genomic profiles were obtained using one of three CGP tests; 49 and 3 patients were evaluated using tissue-based and blood-based assay, respectively. The impact of CGP results on subsequent treatment selection in clinical practice and correlations between representative gene alterations and patient characteristics or responses to immunotherapy were evaluated.

The most frequently observed variants were TERT mutations, followed by CTNNB1, TP53, ARID1A, and MYC mutations. Potentially druggable gene alterations were observed in 45 patients (87%), and 34 patients (65%) were recommended to receive treatments based on specific gene alterations by a molecular tumor board. Treatments were covered by health insurance in 13 patients (25%). Five patients (10%) received the recommended treatment by the date of data cut-off. There were no differences in the efficacy of immunotherapy with respect to mutation status in hTERT, CTNNB1, TP53, ARID1A, and MYC.

The results of the present study suggested that druggable gene alterations may provide useful information not only in proposing alternative treatment after standard of care but also in selecting second-line targeted treatments after immunotherapy for patients with advanced HCC.

This article reviews surveillance for the detection of early stage hepatocellular carcinoma, covering the rationale for surveillance, optimal selection of persons needing surveillance, methods and frequency of screening, strategies for addressing barriers to surveillance, and trends for future improvement in surveillance leading to more effective cancer control and improved patient outcomes. The importance of integrating liver cancer surveillance as a core component of national public health programs is emphasized. The impact of emerging technologies for identifying persons at risk, stratifying individual risk to improve the cost-effectiveness of surveillance programs, and improving the performance, accessibility, and convenience of surveillance are discussed.

Existing hepatocellular carcinoma (HCC) prediction models for the general population without traditional risk factors for chronic liver disease are limited. This study aimed to develop an HCC prediction model for individuals lacking these traditional risk factors.

The total of 138 452 adult participants without chronic viral hepatitis or significant alcohol intake who underwent regular health checkup at a tertiary hospital in South Korea were followed up for the development of HCC. Risk factors for HCC development were analyzed using Cox regression analysis, and prediction model was developed using the risk factors.

Significant predictors of HCC development included older age, male sex, higher body mass index, presence of diabetes mellitus, and levels of aspartate aminotransferase, total cholesterol, and platelet count. A new HCC prediction model using these variables was developed. Harrell's concordance index and Heagerty's integrated area under the receiver operating characteristics (AUROC) curve of the model were 0.88 (95% confidence interval [CI] 0.85-0.91) and 0.89 (95% CI 0.86-0.91), respectively. The 5- and 10-year AUROC were 0.89 (95% CI 0.88-0.89) and 0.87 (95% CI 0.87-0.88), respectively. This model significantly outperformed the FIB-4 scoring model in predicting HCC and effectively stratified individuals into low-, intermediate-, and high-risk groups with significantly different cumulative incidences of HCC.

The new model, based on clinical parameters, provides a valuable tool for clinicians to stratify HCC risk in the general population without risk factors for chronic liver disease.

Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.

To assess the relationship between survival outcomes and subtypes of radiological progressive disease (PD) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atezo/Bev).

A total of 462 patients with Atezo/Bev-treated HCC diagnosed with radiological PD during follow-up were enrolled. PD was classified into three categories: progression or emergence of intrahepatic lesions (PD-IH), macroscopic vascular invasion (PD-MVI), and extrahepatic spread lesions (PD-EHS). We defined PD-multiple as the presence of two or more PD categories. Subsequent analysis was categorized into the "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" groups.

The median progression-free survival (PFS) durations for patients with PD-IH, PD-MVI, PD-EHS, and PD-multiple were 5.3, 3.2, 3.9, and 3.5 months (p = 0.003). Patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" had median PFS of 5.2 and 3.5 months (p < 0.001). Median overall survival (OS) for PD-IH, PD-MVI, PD-EHS, and PD-multiple was 22.3, 15.1, 19.4, and 14.2 months (p = 0.002). The OS for patients with "PD-IH or PD-EHS" and "PD-MVI or PD-multiple" was 21.4 and 14.5 months (p < 0.001). Multivariate analysis demonstrated that ECOG-PS ≥ 1 (hazard ratio (HR), 1.508), α-fetoprotein levels ≥ 100 ng/mL (HR, 1.293), albumin-bilirubin grade ≥ 2 (HR, 1.573), liver cirrhosis (HR, 1.361), and PD subtypes PD-MVI or PD-multiple (HR, 1.735) were independently associated with OS.

Patients with HCC undergoing Atezo/Bev treatment, diagnosed with PD-multiple (not solely based on IH or EHS) or PD-MVI, experienced poor prognosis, specifically in terms of OS.

Background/Objectives: Atezolizumab and bevacizumab combination therapy has been established as a standard of care for first-line treatment; however, its efficacy and safety have not been fully evaluated for patients previously treated with systemic therapy. Methods: In this phase II trial, patients with advanced hepatocellular carcinoma previously treated with lenvatinib were enrolled to receive a dose of 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, disease control rate, subsequent therapy, and frequency of adverse events. The threshold and expected progression-free survival were 3 and 6.8 months, respectively. Considering a one-sided significance level of 0.05 and a statistical power of 80%, the minimum required sample size was 26 patients. Results: The median progression-free survival from the start of treatment was 9.70 [90% confidence interval, 5.10-14.24] months, and the lower limit of the 90% CI was above the predefined threshold. The objective response and disease control rates were 34.6% and 73.1%, respectively. Sixteen patients (61.5%) received subsequent therapies, and the median overall survival was 17.23 [90% confidence interval, 13.18-27.85] months. Severe adverse events, adverse events leading to treatment delays, and adverse events leading to treatment discontinuation occurred in eight (30.8%), fourteen (53.8%), and five (19.2%) patients, respectively, and no treatment-related deaths occurred. Conclusions: Atezolizumab and bevacizumab combination therapy is effective and can safely be administered to patients with advanced HCC previously treated with lenvatinib.

The EASL diagnostic algorithm for hepatocellular carcinoma, currently in use, dates back to 2018. While awaiting its update, numerous advancements have emerged in the field of hepatocellular carcinoma imaging. These innovations impact every step of the diagnostic algorithm, from surveillance protocols to diagnostic processes, encompassing aspects preceding a patient's inclusion in surveillance programs as well as the potential applications of imaging after the hepatocellular carcinoma diagnosis. Notably, these diagnostic advancements are particularly evident in the domain of magnetic resonance imaging. For example, the sensitivity of ultrasound in diagnosing very early-stage and early-stage hepatocellular carcinoma during the surveillance phase is very low (less than 50%) and a potential improvement in this sensitivity value could be achieved by using abbreviated protocols in magnetic resonance imaging. The aim of this review is to explore the 2024 updates in magnetic resonance imaging for hepatocellular carcinoma, with a focus on its role in surveillance, nodular size assessment, post-diagnosis imaging applications, and its potential role before the initiation of surveillance.

Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients.

Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT.

Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively.

LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation.

This retrospective study aimed to investigate the role of an additional high mechanical index (MI) setting scan during the post-vascular phase (PVP) in detecting deep-seated hepatocellular carcinoma (HCC) lesions.

A total of 805 confirmed HCCs, which underwent Sonazoid-based contrast-enhanced ultrasound (CEUS) between January 2014 and October 2021, were included. Low MI scan was initially employed for lesion detection during the PVP, followed by high MI scan. Propensity score matching (PSM) was utilized to address confounding variables.

Of the 805 study lesions, 668 were detected as perfusion defects at the initial low MI setting, while 137 remained undetected. Among these 137 undetected lesions, 77 were identified at the subsequent high MI setting, whereas 60 remained undetected. Lesions that were larger (18.69 ± 11.27 mm vs. 16.55 ± 7.42 mm, p = 0.006), more superficial (6.06 ± 2.41 cm vs. 7.40 ± 2.74 cm, p < 0.001), and hypoechoic (482/668 vs. 62/137, p < 0.001) were detectable at the initial low MI setting. Male patients benefited more from the additional high MI scan (63/97 vs. 14/40, p < 0.001). Lesions identified with additional high MI were larger (18.30 ± 8.76 mm vs. 14.30 ± 4.34 mm, p < 0.001) and deeper than undetected ones (8.48 ± 2.48 cm vs. 6.02 ± 2.43 cm, p < 0.001). After PSM, depth was shown to be an independent predictor in multivariate analysis (odds ratio: 1.557, 95% confidence interval: 1.249-1.941). The depth cutoff was 7.75 cm, with a sensitivity of 0.681, specificity of 0.851, and area under the curve of 0.774.

The additional high MI setting scan during the PVP of Sonazoid-based CEUS leads to enhanced detection of deep-seated HCCs.

Large language models (LLMs) offer opportunities to enhance radiological applications, but their performance in handling complex tasks remains insufficiently investigated.

To evaluate the performance of LLMs integrated with Contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) in diagnosing small (≤20mm) hepatocellular carcinoma (sHCC) in high-risk patients.

From November 2014 to December 2023, high-risk HCC patients with untreated small (≤20mm) focal liver lesions (sFLLs), were included in this retrospective study. ChatGPT-4.0, ChatGPT-4o, ChatGPT-4o mini, and Google Gemini were integrated with imaging features from structured CEUS LI-RADS reports to assess their diagnostic performance for sHCC. The diagnostic efficacy of LLMs for small HCC were compared using McNemar test.

The final population consisted of 403 high-risk patients (52 years ± 11, 323 men). ChatGPT-4.0 and ChatGPT-4o demonstrated substantial to almost perfect intra-agreement for CEUS LI-RADS categorization (κ values: 0.76-1.0 and 0.7-0.94, respectively), outperforming ChatGPT-4o mini (κ values: 0.51-0.72) and Google Gemini (κ values: -0.04-0.47). ChatGPT-4.0 had higher sensitivity in detecting sHCC than ChatGPT-4o (83%-89% vs. 70%-78%, p < 0.02) with comparable specificity (76%-90% vs. 83%-86%, p > 0.05). Compared to human readers, ChatGPT-4.0 showed superior sensitivity (83%-89% vs. 63%-78%, p < 0.004) and comparable specificity (76%-90% vs. 90%-95%, p > 0.05) in diagnosing sHCC.

LLM integrated with CEUS LI-RADS offers potential tool in diagnosing sHCC for high-risk patients. ChatGPT-4.0 demonstrated satisfactory consistency in CEUS LI-RADS categorization, offering higher sensitivity in diagnosing sHCC while maintaining comparable specificity to that of human readers.

Ablation is one of the main methods for local treatment of hepatocellular carcinoma (HCC). Different from radiofrequency ablation (RFA), microwave ablation (MWA) is not limited by tissue conductivity, and can use multiple electrodes at the same time to improve ablation efficiency. In addition, MWA can form a larger ablation area, which makes it possible to completely ablate large HCC. However, MWA may be incomplete due to factors such as larger tumors or tumors in high-risk areas. The mechanism by which the cellular and tumor immune microenvironment (TIME) is involved in the in vitro effects of incomplete microwave ablation (iMWA) needs to be further elucidated.

H22 tumor-bearing C57BL/6 mice were treated with iMWA with several combinations of ablation power and time duration. The effects of iMWA on the genes of HCC cancer cells and the TIME were investigated by RNA sequencing, mass cytometry, immunohistochemistry, and immunofluorescence. The effect of iMWA in combination with anti-Gr-1 on HCC tumor growth was also evaluated.

Thermal stress generated by iMWA induced coagulative necrosis and apoptosis in the region of the ablation center of HCC. RNA sequencing analysis showed that iMWA can boost chemokine CXCL5, which was further confirmed by quantitative real time polymerase chain reaction (qRT-PCR). Mass cytometry results showed that relative to Ctrl group, iMWA-treated led to decreased CD4+ T, CD8+ T, Natural killer (NK), macrophages including both M1 and M2 types but increased monocytes and bone marrow-derived suppressor cells (MDSC). Therefore, inhibiting MDSC is the main target in the later stage of iMWA. In vivo results showed that the tumor volume and weight of iMWA+ anti-Gr-1 group were significantly reduced compared with iMWA+ anti-IgG group. In addition, the merged expressions of CD11b and Gr-1 proteins were found reduced in the iMWA+ anti-Gr-1 group compared with the iMWA+ anti-IgG group by immunofluorescence staining. Immunohistochemistry suggested that CD8 was enriched in the iMWA+ anti-Gr-1 group but not in the iMWA+ anti-IgG group.

Our data suggests that iMWA and Gr-1 blocking combined therapy can further inhibit HCC growth and significantly improve the CD8+ T cells in the mouse subcutaneous tumor model, which brings good news to HCC patients.

Durvalumab plus tremelimumab (Durva/Treme) has recently been approved as a first-line or later-line treatment for patients with unresectable hepatocellular carcinoma (u-HCC) in Japan. We assessed the real-world outcomes of Durva/Treme for u-HCC, with a focus on treatment efficacy and safety.

We retrospectively evaluated 22 patients with u-HCC treated with Durva/Treme at Iwate Medical University during the period from 2023 to 2024, with a comparison of the clinical outcomes between patients who received Durva/Treme as first-line and later-line treatments. We further evaluated changes in the modified albumin-bilirubin (mALBI) grade during treatment.

There were 10 patients in the first-line group and 12 patients in the later-line treatment group. During the follow-up with a median duration of 7.6 months, the median progression-free survival (first-line versus later-line: 4.7 months versus 2.9 months, p = 0.85), the objective response rate (0.0% versus 16.7%, p = 0.48), the disease control rate (60.0% versus 58.4%, p = 1.00), and the incidence of any adverse event (50.0% versus 75.0%, p = 0.38) were not statistically different between the two groups. The changes in the mALBI scores were not statistically significant (p = 0.75).

Durva/Treme may be effective and safe for patients with u-HCC, even in patients who receive Durva/Treme as a later-line treatment.

The Fontan operation, which directly connects the superior and inferior vena cava to the pulmonary artery, is a palliative surgery for children with a functional or anatomic single ventricle. This procedure leads to hemodynamic changes (Fontan circulation) in patients, who tend to develop congestive hepatic fibrosis characterized by sinusoidal fibrosis and dilatation beginning approximately 10 years after the procedure. In addition, in the context of severe fibrosis and cirrhosis, hepato-gastrointestinal complications including hepatocellular carcinoma, focal nodular hyperplasia, and portal hypertension can arise. Fontan-associated liver disease (FALD) encompasses the broad spectrum of liver alterations secondary to postoperative hemodynamic changes, and the effective management of FALD requires contributions from specialists in hepatology, gastroenterology, surgery, radiology, histopathology, and pediatric and adult cardiology. In this article, we outline the pathogenesis of FALD and discuss the importance of a multidisciplinary collaborative approach to its management.

Globally, hepatocellular carcinoma (HCC) is one of the most prevalent and deadly malignant tumors. A recent study proposed disulfidptosis, a novel form of regulated cell death (RCD), offering a new avenue for identifying tumor prognosis biomarkers and developing novel therapeutic targets.

Based on the expression data of 14 disulfideptosis-related genes extracted from public databases, a new molecular classification of HCC called the "disulfidptosis score" was constructed and its relationship to tumor immunity and prognosis was evaluated.

Based on the expression of disulfideptosis-related genes, we performed cluster analysis on HCC samples from the TCGA cohort, which classified these patients into three clusters: A, B, and C, and the differentially expressed genes of different clusters were analyzed. A disulfidptosis score model was constructed by differentially expressed genes associated with prognosis. Univariate and multivariate COX regression analysis showed that disulfidptosis score was an independent prognostic factor for HCC. In addition, in various disulfidptosis score groups, notable disparities were observed concerning the tumor immune microenvironment as well as the expression of immune checkpoint.

Disulfidptosis score have an important role in predicting HCC prognosis and help guide us in providing better immunotherapy options for patients.

Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases.

Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74 years; male patients, 152; Child-Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C, 59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated.

The median observation period was 7.2 months (interquartile range, 3.2-10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, p = 0.028) (median PFS: without vs. with = 5.6 vs. 2.7 months, p < 0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (p = 0.523 and p = 0.038, respectively).

History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.

The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps.

We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC.

A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC.

In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.

There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.

From 2011 to 2018, a cohort of individuals (age ≥70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.

The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20-0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.

In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.

To investigate the relationship between the gut microbiome and the response to anti-PD-1-based combination therapy in unresectable hepatocellular carcinoma (HCC). We aimed to identify potential non-invasive biomarkers and new strategies to modulate immunotherapy in HCC.

In this study, fresh stool samples and clinical data were collected from unresectable HCC patients treated with anti-PD-1-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2020 and December 2021. The patients were divided into two groups based on their response to treatment: the treatment responder group (R group) and the treatment non-responder group (NR group). The composition and diversity of the gut microbiome were bioinformatically analyzed by using the Whole Genome Shotgun strategy, including taxonomic composition analysis, Alpha diversity analysis, Beta diversity analysis, and differentially enriched bacterial taxa analysis. Differentially enriched bacterial taxa between R and NR groups were identified based on the magnitude of the linear discriminant analysis effect size (LEfSe) and analyzed for their impact on the survival of the patient.

A total of 45 eligible patients with unresectable HCC treated with anti-PD-1-based combination therapy participated in this study. The gut microbiological composition and Alpha diversity of patients were not statistically different, but there was a statistically significant difference in Beta diversity between the R and NR groups. (PERMANOVA tests, P = 0.006). We further identified 56 enriched bacterial taxa in the R group and 44 enriched bacterial taxa in the NR group based on the LEfSe analysis (LDA >2.66, P< 0.05). Patients with a high abundance of Collinsella genus, Ruminococcus_AM4211, and Ruminococcus_AF25_28AC had a longer median PFS and median OS compared to those with low abundance (P < 0.05). On the contrary, the median PFS and OS of patients with a high abundance of Bacteroides_AF20_13LB and Veillonella_atypica were significantly shorter than those of patients with low abundance (P < 0.05). The multivariate analysis showed that the abundance of Bacteroides_AF20_13LB and Ruminococcus_ AF25_28AC was independent related factors for PFS, and the abundance of Bacteroides_AF20_13LB was an independent related factor of OS.

The enrichment of specific gut microbiota affected clinical efficacy and survival benefits in HCC treated with anti-PD-1 therapy and may be a promising non-invasive gut microbial biomarker and a new strategy for modulating immunotherapy in HCC.

In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics.

We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group.

Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care.

To develop multiple machine learning (ML) models based on the prognostic nutritional index (PNI) and determine the optimal model for predicting long-term survival outcomes in hepatocellular carcinoma (HCC) patients after local ablation.

From January 2009 to December 2019, we analyzed data from 848 primary HCC patients who underwent local ablation. ML models were constructed and evaluated using the concordance index (C-index), concordance-discordance area under curve (C/D AUC), and Brier scores. The optimal ML model was interpreted using the partial dependence plot (PDP) and SHapley Additive exPlanations (SHAP) framework. Additionally, the prognostic performance of our model was compared with other models.

Alkaline phosphatase, preoperation alpha-fetoprotein level, PNI, tumor number, and tumor size were identified as independent prognostic factors for ML model construction. Among the 19 ML algorithms tested, the Aorsf model showed superior performance in both the training cohort (C/D AUC: 0.733; C-index: 0.736; Brier score: 0.133) and validation cohort (C/D AUC: 0.713; C-index: 0.793; Brier score: 0.117). The time-dependent AUC of the Aorsf model for predicting overall survival was as follows: 1-, 3-, 5-, 7-, and 9-year were 0.828, 0.765, 0.781, 0.817, and 0.812 in the training cohort, 0.846, 0.859, 0.824, 0.845, and 0.874 in the validation cohort, respectively. The PDP and SHAP algorithms were employed for visual interpretation. Furthermore, time-AUC and decision curve analysis demonstrated that the Aorsf model provided superior clinical benefits compared to other models.

The PNI-based Aorsf model effectively predicts long-term survival outcomes after ablation therapy, making a significant contribution to HCC research by improving surveillance, prevention, and treatment strategies.

Early diagnosis and precise treatment of hepatocellular carcinoma (HCC) are crucial for human health. Therefore, addressing the potential markers of HCC, glutathione (GSH) and viscosity, we constructed a fluorescent probe (PG-V) activated cascadically by GSH/viscosity. PG-V possessed excellent photophysical properties and biocompatibility, and could specifically illuminate tumor tissue, achieving fluorescence imaging of HCC, and imaging-guided tumor resection.

The multiparametric nature of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) still leads to uncertainty with its practical management. This study aims to characterize the main posttransplant recurrence patterns of HCC and to explore the therapeutic modalities targeting recurrence.

Consecutive patients who underwent LT for HCC at a single tertiary center were analyzed. The time from first recurrence to death was investigated for each site of presentation. The impact of each recurrence-targeted treatment on survival was studied.

Of 660 patients with HCC, any recurrence occurred in 96 (15.4%) patients with a median time to recurrence of 20.0 months (95% CI: 15.6-23.8). Patients recurred across different patters including solitary distant locations (30.8%, n = 28), liver only (24.2%, n = 22), lung (18.7%, n = 17), multi-organ disease (17.6%, n = 16), and bone (8.8%, n = 8). Multi-organ and bone recurrences had the poorest survival, while solitary distant lesions and pulmonary recurrences had the best outcomes. Each treatment modality carried a distinctive survival.

Patients recurred across 3 patterns with different prognostic implications. The benefit of each treatment option on distinct recurrence patterns appears to be influenced by the biological behavior inherent in the recurrence pattern itself.

Adrenalectomy is the gold standard for canine adrenal tumours, but not always recommended due to patient age, underlying conditions and perioperative mortality. Ethanol ablation is an alternative in human medicine for poor surgical candidates. A 13-year-old neutered female toy-poodle with hypercortisolism presented with severe haematuria. Ultrasonography revealed left adrenal and right kidney tumours. Due to high surgical risk, simultaneous laparotomic right nephroureterectomy and ethanol ablation of the left adrenal tumour were performed. Post-ethanol injection complications included transient hypertension and arrhythmia, which resolved spontaneously. The adrenal tumour size decreased within 2.5 months, and cortisol levels normalised within 8 days, remaining stable for 12 months. No hypercortisolism signs were observed without trilostane until death from renal insufficiency. Autopsy showed that the ablated left adrenal gland was an adrenocortical tumour and had shrunk. Ethanol ablation may be a feasible alternative to adrenalectomy for high-risk canine patients.

While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking.

The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab.

This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge.

Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory.

Hepatocellular carcinoma (HCC) is an extremely rare long-term complication of Budd-Chiari syndrome (BCS) which may occur due to long-term venous congestion causing fibrosis, cirrhosis and subsequent hepatocellular dysplasia or anaplasia. This complication is even rarer in paediatric BCS and warrants early diagnosis for a favourable prognosis. Benign regenerative nodules seen with BCS are difficult to differentiate from malignant nodular lesion of HCC, thereby making serial imaging less sensitive for early diagnosis of HCC in BCS. Surveillance guidelines like adults do not exist in monitoring chronic paediatric BCS due to rarity of this complication. Six monthly serum alpha-fetoprotein monitoring in addition to radiological surveillance improves the sensitivity of early detection of HCC transformation in BCS and should be the way ahead in paediatric BCS as well. We describe a paediatric patient who presented with advanced HCC after 25-month follow-up for BCS.

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.